Quinolizidine alkaloids from plants and their cell suspension cultures

The alkaloid composition of cell suspension cultures and differentiated plants of LUPINUS POLYPHYLLUS was evaluated using quartz capillary gas-liquid chromatography, GLC-MS and FD-MS. Lupanine (97% of total alkaloids), sparteine, 13-angeloyloxylupanine and 13-tigloyloxylupanine were detected in alkaloid extracts of L. POLYPHYLLUS cell suspension cultures. Lupanine, 13-cis and 13-trans-cinnamoyloxylupanine were found in the spent cell culture medium. No significant difference was found in the alkaloid composition of photomixotrophic and heterotrophic cell strains although the alkaloid content was 5 to 10 times higher in photomixotrophic cell strains. In the respective plants we could identify 18 alkaloids which include the following esters of 13-hydroxylupanine: 13-tigloyloxylupanine, 13-angeloyloxylupanine, 13-cis-cinnamoyloxylupanine, 13-trans-cinnamoyloxylupanine, 13-benzoyloxylupanine, 13-(2-methylbutyryl)-oxylupanine; and 13-vanilloyloxylupanine.     

The psychological effects of dopamine-beta-hydroxylase inhibition in normal subjects.

Acute administration of the dopamine-beta-hydroxylase (DBH) inhibitor, fusaric acid, combined with L-dopa, 500 mg, produced discernible psychological abnormalities in normal subjects. These were not found after L-dopa alone, or after placebo. The changes, lasting a few hours, were manifested by significant increases in "total psychopathology," and in a number of subscales on the Brief Psychiatric Rating Scale. Changes were also found in mood ratings on adjective checklists, and inkblot tests. A variety of effects were found on psychiatric interview. Since DBH does not occur in dopamine neurons, it is likely that the psychological effects were due to changes in dopamine or norepinephrine in norepinephrine neurons.     

Marrow regeneration after mechanical depletion

The origin of marrow regeneration after mechanical depletion was reinvestigated in mouse chimeras. The results were compatible with the local origin of stem cells from remnants of incompletely removed marrow, but not with their origin from a common precursor of both bone and hemopoietic cell lines. In transplanted femurs depleted by a modified technique of in vivo evacuation of marrow, hemopoietic regeneration failed to occur. The presence of hemopoietic stem cells in the Haversian canals was thus excluded. The demonstration of ample hemopoiesis with minimal bone formation in nondepleted controls in which bone marrow initially became necrotic provided new evidence that osteogenesis was not a prerequisite of hemopoietic regeneration.     

Hashimoto-Enzephalopathie Steroid-sensitive Enzephalopathie bei Hashimoto-Thyreoiditis

Hashimoto's encephalopathy is a steroid-responsive, relapsing or progressive encephalopathy associated with Hashimoto's thyroiditis. Characteristic clinical features are confusion, seizures, alteration in conscious level, stroke-like episodes, myoclonus, and tremulousness. High CSF protein levels without pleocytosis and a diffusely abnormal EEG are typical findings. Brain CT and MRI and cerebral angiogram are usually normal. We present two case reports of Hashimoto's encephalopathy in 55- and 77-year-old patients who both responded well to steroid therapy, and review the literature.     

Predictors of resource use after acute hospitalization: the Northern Manhattan Stroke Study

OBJECTIVE: To determine demographic and clinical predictors of discharge destinations following acute care hospitalization for stroke in the community of northern Manhattan. METHODS: A group of 893 patients (mean age, 70 +/- 12 years; 56% women; 51% Hispanic, 30% African-American, 19% white) who survived acute care hospitalization for a first ischemic stroke were followed prospectively. Stroke severity was assessed by the NIH Stroke Scale and categorized as mild (< or = 5), moderate (6 to 13), and severe (> or = 14). Polytomous logistic regression was used to determine predictors for rehabilitation and nursing home placement versus returning home. RESULTS: Among the survivors of acute stroke care hospitalization, 611 (68%) patients were discharged to their homes, 168 (19%) to rehabilitation, and 114 (13%) to nursing homes. Patients with moderate and severe neurologic deficits had more than a threefold increased risk of being sent to a nursing home and more than an eightfold increased risk of being sent to rehabilitation. Age over 65 and cognitive impairment were associated with placement to a nursing home (age over 65: OR, 2.4; 95% CI, 1.0 to 5.6; cognitive impairment: OR, 2.9; 95%, CI 1.4 to 5.7), and rehabilitation (age over 65: OR, 1.8; 95% CI, 1.1 to 2.9; cognitive impairment: OR, 2.9; 95% CI, 1.4 to 5.7). CONCLUSION: Our results demonstrated that one-third of patients with acute stroke from the community of northern Manhattan required placement in a temporary or a long-term disability care institution following acute care hospitalization. Severity of stroke is an important factor that influences discharge planning following acute care hospitalization and its reduction can improve health care resource usage.     

Intracerebral abscess caused by Nocardia otitidiscaviarum in a renal transplant patient--cured by evacuation plus antibiotic therapy

We present a 50-year-old female who experienced generalized convulsion 3 months after a successful cadaveric renal transplantation. The first cerebral CT scan indicated cerebral frontal infarction. Repeat CT some days later revealed progressive lesions, and a highly malignant tumor or abscess was suspected. Antifungal and broad-spectrum antibacterial therapy was initiated. Cerebral MRI could not differentiate between these conditions, but a neutrophil granulocyte scan strongly suggested an infectious process. A stereotactic puncture of the frontal lobe was followed by temporary improvement. A severe progressive left-sided hemiparalysis gave indication for a craniotomy with evacuation of the abscess 9 days later. Culture of aspirated pus yielded growth of a gram-positive, rod-shaped bacterium, later identified as Nocardia otitidiscaviarum by sequencing the 16S rRNA. The patient was treated with meropenem plus rifampicin intravenously for 6 weeks followed by oral ciprofloxacin and rifampicin for 2 months. Due to pharmacokinetic interaction with rifampicin, the prednisolone dose was doubled, and the dose of tacrolimus had to be tripled for maintenance of adequate trough concentrations. Five months following cessation of antibiotic treatment, the patient has regained normal strength and function in her left-sided extremities and has a serum creatinine level of about 160 micromol/l (1.8 mg/dl).     

Localized pelvic neuroblastoma: excellent survival and low morbidity with tailored therapy--the 10-year experience of the French Society of Pediatric Oncology.

PURPOSE: To assess the results and morbidity of treatment of children with localized pelvic neuroblastoma (NB). PATIENTS AND METHODS: All consecutive cases of localized pelvic NB registered in the French multicenter prospective studies NBL90 and NBL94 between 1990 and 1999 were reviewed. Resectability was decided on the basis of clinical and radiologic evaluation. In unresectable tumors, primary chemotherapy (combinations of carboplatin-etoposide and vincristine-cyclophosphamide-doxorubicine) was administered before surgery. RESULTS: Forty-seven children (with 26 resectable tumors and 21 unresectable) were included in this study. At the end of treatment, 31 children were in complete remission (66%). Long-term neurologic sequelae were observed in seven patients (15%), directly attributable to surgery in three cases. After a median follow-up of 48 months (range, 13 to 129 months), 44 patients are alive. Six children experienced local relapse; four of these children achieved subsequent remission. The projected overall survival and event-free survival (EFS) rates at 5 years are, respectively, 93% +/- 4% and 84% +/- 5%. Survival of children treated with preoperative chemotherapy are similar to those treated by primary surgery (80% and 88% respectively). The extent of surgical resection seemed to have no influence on the outcome (EFS rates 76% and 89% in case of gross residue and complete resection or microscopic residue, respectively). CONCLUSION: Our data confirm the excellent survival of localized pelvic NBs. Considering the efficacy of preoperative chemotherapy, patients with pelvic NB should be carefully screened for primary surgery. The risk of neurologic impairment during radical excision should be balanced with the good survival of children with minimal residual disease.     

Circulating growth factor levels are associated with tumorigenesis in neurofibromatosis type 1.

PURPOSE: Neurofibromatosis type 1 (NF1) is characterized by systemic development of neurofibromas. Early clinical diagnosis can be ambiguous, and genetic diagnosis can be prohibitively difficult. Dysregulation of a number of growth factors has been suggested to be a mechanism of pathogenesis. This study was performed to assess the contribution of circulating growth factors for diffuse tumorigenesis and the diagnostic value of circulating growth factor identification in serum. EXPERIMENTAL DESIGN: The growth stimulation of neurofibroma-derived cells by serum from NF1 patients was tested, and serum growth factor levels in a cohort of NF1 patients (n = 39) between the ages of 7 and 70 years were analyzed. RESULTS: Concentrations of midkine (MK) and stem cell factor, but not epidermal growth factor, were substantially increased in serum of NF1 patients when compared with healthy controls. Within the NF1 group, MK levels increased dramatically at puberty from an average of 0.79 ng/mL in patients <18 years to 1.18 ng/mL in patients >18 years old. Stem cell factor and MK concentrations above a defined threshold in serum of NF1 patients are of diagnostic benefit for 96% of patients in the cohort tested. Furthermore, serum from NF1 patients enhanced proliferation of human neurofibroma-derived primary Schwann cells and endothelial cells substantially better than normal serum. CONCLUSIONS: Enhanced circulating growth factor levels contribute to diffuse tumorigenesis in NF1 and may provide the basis for molecular diagnosis.     

Risk factors for relapse in clinical stage I nonseminomatous testicular germ cell tumors: results of the German Testicular Cancer Study Group Trial.

PURPOSE: To prospectively assess potential risk factors for relapse in clinical stage I nonseminomatous germ cell tumors of the testis (CS I NSGCT). PATIENTS AND METHODS: From September 1996 to May 2002, 200 patients with CS I NSGCT were prospectively assigned to retroperitoneal lymph node dissection (RPLND), and risk factor assessment was performed within a multicenter protocol. One hundred sixty-five patients had an adequate minimum follow-up of 12 months (mean, 34.5 months) or had pathologic stage II. RESULTS: Pathologic stage II disease was found in 27.9% of patients. Only 0.6% of patients relapsed in the retroperitoneum after confirmation of pathologic stage I disease. With reference pathology, vascular invasion (VI) was most predictive of stage in multifactorial analysis (accuracy, 65.1%). However, the positive predictive value (PPV) of VI to predict patients who have metastatic disease or relapse during follow-up was only 52.7%. With absent VI, low-risk patients had a negative predictive value (NPV) of 76.9%. With a combination of several risk factors, the PPV increased to 63.6% and the negative predictive value increased to 86.5%. CONCLUSION: Even with an optimal combination of prognostic factors and reference pathology, more than one third of patients predicted to have pathologic stage II or relapse during follow-up will not harbor metastatic disease and, therefore, would be overtreated with adjuvant therapy. However, patients at low risk may be predicted at an 86.5% level, and thus, surveillance in highly compliant patients would be a valuable option. For high-risk patients, further reduction of adjuvant treatment is necessary.